Open-source force analyzer with broad sensing range based on an optical pickup unit

Graphical abstract


Force detection module
shows the force detection module consisting of the OPU and the cantilever-based force transducer. The OPU emits a laser with a wavelength of 650 nm, and a built-in voice coil motor actuates an objective lens in the z-axis direction to precisely focus the laser on the mirror. Furthermore, the OPU integrates an astigmatic optical path and a sensor to generate a focus error signal (FES) [13]. While the mirror approaches along the z-axis to a laser focal point, the FES appears as an Sshaped curve (S-curve) (Fig. 2b). The middle part of the S-curve represents a highly sensitive linear signal that monitors the cantilever deflection with a nanometer-scale resolution. Thus, the FES can detect the cantilever deflection caused by an applied force. The DVD OPU has an FES linear range of approximately a few microns.
The cantilever-based force transducer converts the applied force to a structural deflection during the measurement process (Fig. 2c). The applied force F is proportional to the cantilever deflection D, as described in the following formulation [20]: where E c is the Young's modulus of the cantilever, and w c , t c , and l c are the width, thickness, and length of the cantilever, respectively.
Tien-Jen Chang, Line Hagner Nielsen, A. Boisen et al. HardwareX 11 (2022) e00308 The force detection module utilizes different cantilever-based force transducers to detect the applied forces from Newton to micro-Newton scale. Steel shim-based cantilevers can easily be adjusted to fit a suitable measuring force range by selecting the shim thickness and/or adjusting the cantilever length, according to Equation (1). In addition, a commercial microcantilever (AFM probe) can be directly attached to the edge of the steel shim to detect the force on the nano-Newton scale (Fig. 2d).
The force detection module utilizes a microprobe which is a straight pin, an off-the-shelf, standardized electronic component (Fig. 2e). Compared to the centimeter-scale probe on a commercial texture analyzer, this microprobe is suitable for carrying a single micrometer-scale device. Furthermore, within the microscale contact area, the microprobe can increase the reproducibility of the measurements of the micro-Newton mucoadhesion force. Since a fresh mucus tissue has a topography variation in the millimeter range, the centimeter-scale probe cannot uniformly contact the mucus layer. Minimizing the contact area of the probe will reduce the variation from the mucus layer surface, which decreases the uncertainty of contact conditions and increases the reproducibility of the measurements.

Sample-positioning module
A manual linear stage carries the sample, allowing the adjustment of the sample position along the y-axis (Fig. 1a). To approach and withdraw the sample to the microprobe, we used a linear stepper motor (LTM 60-25, OWIS GmbH, Staufen, Germany) that provides a total travel distance of 25 mm along the z-axis. The stepper motor moves 5 lm per step. By a max- Fig. 1. Development of a force analyzer using a DVD optical-pickup-unit (OPU) to detect the cantilever force transducer with the applied force from Newton to nano-Newton. a) Diagram of the force analyzer, including force detection and sample-positioning modules and a control system. b) Detailed diagram of force detection module assembled by an OPU, a cantilever force transducer, and a microprobe. c) Photograph of the OPU force analyzer. d) Detailed photograph of force detection module. imum of 128 divided stepper motor drivers, the stage reaches the highest positioning resolution of 40 nm for a single substep. Within the highest positioning resolution setting, the motor has a maximum positioning speed of 1.56 mm/s.

Control system
An embedded controller (myRIO-1900; National Instruments, Austin, TX, USA) is connected to an OPU controller and a motor control board (Fig. 1a). The OPU controller calculates the FES and drives the voice coil motor. The motor control board controls the stepper motor for the sample positioning. The embedded controller communicates with a computer through a graphical user interface program to control the force measurement process.
In summary, the presented OPU force analyzer offers the following advantages: Nanometer-scale sensitivity and a broad force measuring range from Newton to nano-Newton. Increased reproducibility for mucoadhesion force characterization of microscale devices by the microprobe. Cost-effective components and an open-source design provide users with easy customization for various force measurement tasks, such as indention and compression tests.

Design files
The design files were drawn using computer-aided design (CAD) software SolidWorks 2014 (Dassault Systèmes Solid-Works Corporation, Massachusetts, USA). All the design files can be downloaded from the linked Mendeley data repository.  The DVD OPU focuses a 650-nm-wavelength laser beam on a mirror to sense the deflection of the cantilever force transducer. b) Focus error signal (FES) presents an S-curve, while displacing the mirror along the z-axis direction. The S-curve presents a highly sensitive linear range. c) The cantilever deflection D caused by the applied force F. The force detecting range of the cantilever force transducer is defined by the thickness (t c ) and length (l c ) of the cantilever. The length of the cantilever is modified by shifting four rectangle magnets along the y-axis direction. d) Installation of microcantilevers for nano-Newton scale force measurement. e) SEM image of the microprobe (scale bar represents 500 lm).

Software and firmware
The firmware and the operation program were edited and compiled using the LabVIEW 2016 software (National Instruments, Austin, TX, USA). A compressed file containing all the programs is available in the Mendeley data repository listed in the following table. All unzipped program files are located in the same folder to maintain the original data path.

Build Instructions
The assembly process of the mucoadhesion force analyzer requires instant glue and double-sided tape to firmly bond the components. The screw holes of the 3D printed parts are designed for a direct screw-in fixture; therefore, hole thread tapping is not required. One needs to be aware of all the required parts of 3D printing before the assembly process.
Cantilever force transducer assembly (Fig. 3b) 1. Components needed: 1 Â steel shim 0.1, 4 Â rectangle magnets, 2 Â cylinder magnet, 1 Â straight pin, 1 Â probe base, and 1 Â mirror. 2. Cut 35 mm of the steel shim 0.1 as a cantilever force transducer. 3. Glue a mirror on the edge of the cantilever 4. Below the mirror, glue a cylinder magnet on the bottom side of the cantilever. 5. Fix the cantilever to a target length (l c ) with four rectangle magnets. 6. Cut 10 mm of the straight pin as a microprobe. 7. Glue the microprobe in the cavity of the probe base, avoiding the protrusion of the microprobe from the backside. 8. Glue a cylinder magnet on top of the probe base. 9. Place the cantilever force transducer on the magnet track and align the mirror to the OPU laser focal spot area. 10. To prepare different thickness cantilevers, repeat the assembly process 2-5. 11. The cantilever length and thickness influence the force measurement range. The force calibration for the reference is presented in Section 7.2.
Microcantilever force transducer assembly (Fig. 3c) 1. Components needed: 1 Â steel shim 0.3, 4 Â rectangle magnets, and 1 Â microcantilever. 2. Cut 20 mm of the steel shim 0.3. 3. Bend it as a microcantilever holder (Fig. 3c). 4. Fix a microcantilever on the edge of the microcantilever holder with double-sided tape. 5. Fix the cantilever with four rectangle magnets. 6. Place the microcantilever holder on the magnet track and align the microcantilever to the laser focal spot area.
Assembly of the whole system ( Fig. 4) 1.  2. Fix four bases on the four corners of the optical breadboard with eight M6Â16mm screws (Fig. 4a). Slightly adjust the vertical position of each base to allow the system to stably stand on a flat surface. 3. Fix the OPU controller base on the optical breadboard with four M6Â16 mm screws. 4. Fix the linear stepper motor on the optical breadboard with four M4Â25mm screws, four M4 nuts, and four M4 washers ( Fig. 4a and b). 5. Fix the platform adaptor on the platform of the linear stepper motor with four M4Â8mm screws. 6. Fix the platform on the platform adaptor with six M4Â8mm screws. 7. Fix the manual linear stage on the platform with four M6Â10mm screws. 8. Fix the force detection module on the optical breadboard with two M6Â16mm screws and two M6 washers (Fig. 4a and  c). 9. Fix the OPU controller on the OPU controller base with four M3Â6mm screws (Fig. 4d).
Operation Instructions (Fig. 6) 1. Switch on the myRIO-1900, the power supply, and the OPU controller power (Fig. 5b). 2. Open a LabVIEW project named ''OPU force analyzer" and a Vi named ''OPU force analyzer." Then, press the ''run" button to start the program. The FES appears in the signal chart. 3. Adjust a voice coil motor-z knob (on the OPU controller, Fig. 5b) clockwise/counterclockwise to shift the objective lens upward/downward. Utilize the knob to adjust the vertical position of the laser spot. 4. Focus the laser spot directly on the mirror on the top side of the cantilever force transducer (Fig. 2a) or the microcantilever (Fig. 2d). 5. Adjust the knob and shift the FES to the center of the linear range (Fig. 2b). 6. Place a sample on the manual linear stage. 7. Activate the linear stepper motor by clicking the ''Enable" button, and move the sample to a suitable position using the ''move up" and ''move down" buttons. 8. Set the measurement parameters, ''contact force," ''contact time," ''retreat point," and ''speed." The retreat point represents the stop position while withdrawing the sample from the microprobe. 9. Set the ''force sensitivity (S .F. )" to convert the FES voltage to a force reading value. The S .F. can be referred to in Section 7.2 calibration process. 10. Click the ''start" button to enable the measurement procedure. The signal chart plots and records the measured force curves. 11. After the measuring process, press the ''save" button to save the recorded signal chart.

Validation and characterization
Linear range and noise analysis (Fig. 7) It is crucial to characterize the linear range of the S-curve and the FES noise level before sensing the cantilever-based force transducer. Fig. 7a shows the S-curve with the upper and lower signal cutoffs (due to signal saturation). The S-curve linear range was further analyzed, as shown in Fig. 7b. The full range inner S-curve (blue line, 8.68 to À9.98 V) has an R-squared value of 0.982, which is unsuitable for an accurate displacement measurement. When reducing the sensing range from 3.76 to À9.98 V, the R-squared value is 0.999, showing much better signal linearity. Thus, the OPU force analyzer is working at this linear range (red line) with an effective displacement sensing range of 1.07 lm and a sensing sensitivity of 0.077 nm/mV.
The FES from the OPU controller has a root mean squared (RMS) noise level of 28 mV, which corresponds to a displacement sensing noise of 2.2 nm. Further, we investigated the combined system noise level by focusing the focal spot on the mirror on the top side of the cantilever. Under these conditions, the FES signal containing environmental vibration noise and electrical noise from the OPU controller was processed by a 100 Hz low-pass filter (Fig. 7c). Hence, the FES used for detection has an RMS noise of 64 mV, corresponding to a displacement sensing noise of 4.9 nm. A Gaussian distribution statistical analysis (Fig. 7d) shows that the FES signal noise has a mean value and standard deviation of 0.972 V and 0.032 V, respectively. Furthermore, a fast Fourier transform of the signal shows an 11.90 Hz and a 59.18 Hz noise caused by environmental vibration and electrical noise, respectively (Fig. 7e). The combined system noise could be reduced by further improvements, such as strengthening the system rigidity, isolating environmental vibration, and shielding sensitive signals.

Force transducers calibration and estimation
After the signal sensitivity characterization, the OPU force analyzer can monitor different cantilever-based force transducers to reach different target force measurement ranges.
Newton to milli-Newton force transducer calibration (Fig. 8) To achieve a force-sensing range from the Newton to milli-Newton scale, five 0.3 mm steel shims were stacked and glued into a 1.5 mm-thick cantilever transducer. The length of the cantilever was adjusted to 8.26 mm. The microprobe was attached to the free end of the thick cantilever. A digital scale (JoeFrex Corp., Huston, United States) at the sample stage was driven upward to contact the microprobe. The digital scale was calibrated by a precision balance (see Appendix A. Supplementary material Figure S1). Three contact force (translated from the weight) values from the digital scale were used to calibrate the FES, with a force sensitivity (S .F. ) of 0.086 N/V. The thick cantilever transducer enables the OPU force analyzer to measure a force ranging from 1.1 N to 5.50 mN. Milli-Newton to micro-Newton force transducers calibration (Fig. 9) A different method was used to calibrate the cantilever force transducers for the milli-Newton and micro-Newton ranges. A standard steel shim (t c = 0.3 mm) was used as a milli-Newton cantilever transducer. Fig. 9a shows a force corrector A attached to the bottom of the cantilever. Different known weights from 2559.8 to 122.9 mg (weighted by precision balance XPE26, Mettler Toledo, Greifensee, Switzerland) were loaded on the force corrector A (Fig. 9b). The force corrector B on the sample stage was driven upward, and the weight was unloaded. The weight loading and unloading processes were monitored by the FES (Fig. 9c), which was then calibrated with multiple cantilever lengths (l c = 8.26, 13.3, and 18.4 mm) settings (Fig. 9d). A micro-Newton cantilever transducer is a thin steel shim (t c = 0.1 mm) that is calibrated using the same process with the known weights from 60.98 to 2.74 mg (Fig. 9e). Both the milli-Newton and micro-Newton cantilever transducers have linear correspondences between the FES and weight at different l c length settings.
The milli-and micro-Newton cantilever transducers are primarily used for single microdevice mucoadhesion force measurements, and therefore, we further analyzed the force-sensing ranges and sensitivities of both transducers with different cantilever length settings. Fig. 9f shows the force-sensing range, sensitivity, and resolution of the milli-Newton transducer, which can sense a maximum force of 111.56 mN and the highest resolution of 0.05 mN. The micro-Newton transducer can reach a maximum force limit of 3,271.3 lN and the highest resolution of 3.5 lN (Fig. 9g). Users can reference the abovementioned l c and t c parameters to find a suitable force-sensing range for their experiments. Besides, this measurement system performs a reproducibility of 1.42 lN for measuring the adhesion force of a single microdevice in the micro-Newton force range (see Appendix A. Supplementary material Table S1).
Nano-Newton force transducer sensitivity estimation (Fig. 10) For nano-Newton range force sensing, we utilized an AFM probe (PPP-CONT, Nanosensors TM , Neuchatel, Switzerland) containing a microcantilever with an l c = 450 lm, w c = 50 lm, and t c = 2 lm, and a tip (height = 15 lm) at the bottom side of the microcantilever. The nanoscale laser spot of the OPU is beneficial for monitoring the microcantilever, which can function as a nano-Newton force transducer. The AFM probe was attached to the microcantilever holder using double-sided tape ( Fig. 10a and b). The OPU laser can directly focus on the microcantilever (Section 6. ''Operation Instructions" step 4 to align the laser focal spot). A silicon substrate on the sample stage was positioned upward and touched the tip during the process. The stage further moved 200, 400, and 800 nm, while the FES monitored the microcantilever deflection simultaneously. Since the microcantilever has a typical force constant of 0.2 nN/nm, the OPU force analyzer can reach an estimated force sensitivity of 15.5 nN/V and a resolution of 0.99 nN (Fig. 10c).

Preliminary study of mucoadhesion force alteration while time and moisture escape
While characterizing the mucoadhesive force of microdevices towards an intestinal mucus layer, the dehydrating effect caused the mucus layer to be more adhesive and increased the measured mucoadhesion force. The dehydrating effect usually becomes severe over time. Two experimental groups were set with a dry and wet sample to determine how time affected the adhesive behavior of the mucus layer. The mucoadhesive force of a slice of porcine small intestinal tissue was measured approach/withdrawal speed of 0.156 mm/s (Fig. 11a). The measurements were performed at room temperature of 22.5 ± 2. 5°C and relative humidity of 45 ± 5 %. The cantilever force transducer applied was 0.1 mm in thickness and 8.26 mm in length.
The mucoadhesion measurements for the dry and wet groups are shown in Fig. 11b and c, respectively. The results indicate that the mucoadhesive force of the groups increased with time. In the first 20 min, both groups had a relatively stable mucoadhesive force (Fig. 11d). The mucoadhesive force in the dry group continuously increased for 60 min. Finally, the  mucoadhesive force peaked at approximately 130 % compared with the initial level. The mucoadhesion force of the wet group increased by approximately 57 % within 60 min. Furthermore, the slope of the force growing curve of the dry group (with a displacement of 0.3 mm) fluctuated at various time points (Fig. 11b). The wet group had the same slope (Fig. 11c). This preliminary study indicated that PBS treatment maintained mucus layer stability during mucoadhesive force measurements. In addition, the mucus layer behaved stable within 20 min.

Mucoadhesive force measurement of microcontainers
Microcontainers (MCs) are polymeric cylindrical microdevices intended for oral drug delivery [1,2]. They have a cavity for drug loading on the top side, and since only one side is open, they can provide unidirectional drug release through the GI tract to increase drug absorption efficiency. The transit mechanism has been investigated using an ex vivo intestinal perfusion model and animal studies [7,21]. However, the mucoadhesion force of a single MC has not been thoroughly studied because of the limited resolution of the conventional texture analyzer.
In this study, the OPU force analyzer was used to measure the ex vivo mucoadhesive force of a single SU-8 MC using a piece of porcine small intestinal tissue. The adhesion of PBS buffer to the MC was also investigated for comparison. The MC was glued to the tip of the microprobe for contact with the sample (mucus and PBS) with the top and bottom sides, respectively ( Fig. 12a and b). Fresh porcine small intestine tissue was stored in a freezer under À17°C. The tissue was thawed at room temperature for 20 min and sliced into a small piece of approximately 20 mm in length. The tissue was opened using scissors and placed on the sample stage with the mucosa side upward (Fig. 12c). In addition, a PMMA plate was placed on the sample stage to carry the PBS buffer. The pool of PBS buffer appeared to be an approximately 30-mmdiameter round and a flat surface in the center. The MC contacted the center part of PBS buffer pool for measuring the adhesive force. The parameters were set to a constant speed of 0.078 mm/s and a contact time of 1 s. Four measurements of each sample of both the top and bottom sides of the MC were implemented.
The results show that the adhesive force curve of the PBS to MC presents a right triangle (Fig. 12d). The adhesive force proportionally increased to an average peak force of 93.7 lN (top) and 91.6 lN (bottom) in the sample withdrawal process.
As the PBS separates from the MC, the force curve returns to its original level. The mucus presented a symmetrical hill profile with an average peak force of 75.5 lN (top) and 75.1 lN (bottom) in the middle (Fig. 12e). Instead of sudden detachment, the mucus gradually separated from the MC. In Fig. 12f, the comparison indicates that the MC is more adhesive to the PBS buffer than the mucus. The measurements of the PBS buffer show relatively low variation owing to the material uniformity of the PBS buffer. In contrast, the measurements of mucoadhesive force show a high deviation. Both sides of the MC exhibit the same adhesion level, since the MC possesses a symmetrical structure on both sides. The fact that the adhesive force of the top side shows a higher degree of variation is probably because the edge of the cavity on the top side easily causes uncertain contact with mucus.

Conclusion
The OPU force analyzer utilized different cantilever force transducers that provided a broad range of force measurements ranging from 1.1 Newton to 0.99 nano-Newton. The sample-positioning module provided a 25-mm travel distance and 40-nm resolution, which had high flexibility for a wide variety of sample measurements. The OPU force analyzer could successfully measure the micro-Newton scale interaction force curves between a single MC and the intestinal mucus layer under different conditions. The simple, cost-effective, and open-source OPU force analyzer has a high potential for various force measurement applications in different fields. The noise of FES while measuring is approximately twice of original FES due to the environmental vibration and electrical noise. Hence, the OPU force analyzer has the potential to further extend the force range down to the pico-Newton scale by minimizing the noise of FES. The feasible ways to reduce electrical noise and interference from the environment are strengthening the mechanical rigidity, implementing an anti-vibration structure, and improving the design of electronic circuits and power source.

Ethics statements
All ethical guidelines were complied with in this work.

Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.